tbuckley/cabot-search huggingface dataset:
Abstract 10186: Accuracy Study of Wearable Devices for Monitoring Blood Pressure in Acute Stroke Patients
Authors: Hong Chang, Peipei Li, Siying Tian, Xinyue Zhang, Jie Zhao
Journal: Circulation (2022)

Objective: The fluctuations of blood pressure in the acute stage of stroke are associated with neurological deterioration and poor prognosis. Although continuous monitoring of blood pressure changes becomes possible with the emergence of wearable blood pressure monitoring equipment, the accuracy of the equipment is still in doubt. Here, the accuracy of the optoelectronic-based wearable device for blood pressure monitoring in hospitalized patients with acute stroke were investigated and verified. Methods: Thirty-five acute stroke patients in the Department of Neurology of a teaching hospital were recruited. With the blood pressure values measured by bedside ECG monitor as the gold standard, wearables devices (wearable wrist watch) and bedside ECG monitors were monitored sequentially the same upper limb at the same time and recorded every 2 hours during the first 24 hours of admission. Receiver operating characteristic (ROC) curves were employed to determine the optimal cut off points and tests of sensitivity, specificity, kappa coefficients were conducted. Results: The average age of participants (male 17, female 18) was 61.91 ±8.72 years. 414 groups of blood pressure values were measured and ranged from 74/41 to 221/124 mmHg. The kappa value of systolic blood pressure (SBP) measured by wearable wrist watch and bedside ECG monitor was 0.768, with 89.1% sensitivity and 87.7% specificity (Table 1-A). And the kappa value of diastolic blood pressure (DBP) was 0.648, with 94.6% sensitivity and 67.9% specificity (Table 1-B). The area under ROC curve for SBP diagnosis and DBP diagnosis of wearable wrist watches were 0.941 ( p &lt; 0.001, Figure 1-A) and 0.939 ( p &lt; 0.001, Figure 1-B) respectively. There was no significant difference in SBP and DBP between these two methods ( p &gt;0.05, Table 3). Conclusions: The accuracy of wearable wrist watch for measuring patient blood pressure with acute stroke is good enough for ambulatory blood pressure monitoring of acute stroke patients.
Abstract 10436: Spontaneous Hemopericardium After Rivaroxaban
Authors: Saadia Nawal, Haneen Ismail, Jannet F Lewis
Journal: Circulation (2022)

Direct oral anticoagulants (DOACs) such as rivaroxaban have become the drugs of choice when treating a variety of conditions requiring anticoagulation. We describe a case of a patient found to have hemopericardium with tamponade physiology on a routine echo ordered for evaluation of tachycardia. A 49-year-old man with systemic hypertension was found to have a right lower lobe pulmonary embolus (PE) during a hospitalization for diabetic ketoacidosis complicated by pneumoperitoneum s/p small bowel resection. Rivaroxaban 15 mg twice daily was initiated for treatment of PE. On day 2 rivaroxaban, patient became tachycardic. Chest CT showed a small to moderate pericardial effusion with pericardial enhancement. On day 7, a echo showed trivial pericardial effusion without hemodynamic compromise. Tachycardia persisted after hospital discharge, but patient was otherwise asymptomatic. Patient transitioned to rivaroxaban 20 daily after 3 weeks. Outpatient echo done 2 months after discharge showed a large pericardial effusion with tamponade physiology. Patient was instructed to go to hospital for admission. Labs were significant for Hgb 7.8, and elevated PT 52.50, INR 4.5 and PTT 33.80. Rivaroxaban was held, and patient was given 2 units FFP, Vitamin K 10 mg oral, Kcentra 4208 units and 2 units pRBCs. Patient underwent a pericardiocentesis with removal of 600 cc of sanguineous fluid. Fluid analysis was consistent with hemorrhagic effusion. Repeat echo showed a small residual, anterior pericardial effusion with constrictive physiology. Patient was discharged on reduced dose of rivaroxaban 10 daily and Vitamin K 5 mg daily until outpatient follow up. Our case of hemopericardium occurring in a middle-aged man without confounding issues is unusual. Although hemopericardium with DOACs have been reported, the majority of cases have occurred in patients with pre-disposing risk factors. A systemic review of 26 cases by Asad, et al. described risks associated with cardiac tamponade with DOACs. The incidence of hemopericardium and tamponade appeared highest in elderly men with renal and coagulation abnormalities. Our case highlights the importance of vigilance in patients on DOACs who present with subtle symptoms suggestive of hemodynamic compromise or instability.
Abstract 10476: Impact of C-Reactive Protein Levels on Lipoprotein(a)-Associated Coronary Artery Disease and Aortic Stenosis Risk in Apparently Healthy Individuals
Authors: Arnaud Girard, Emilie Gaillard, Audrey Paulin, Rishi Puri, Christian Couture, Nicholas J Wareham, Philippe Pibarot, Marie-Annick Clavel, Erik S Stroes, Patrick Mathieu, Sebastien Theriault, Matthijs Boekholdt, Benoit Arsenault
Journal: Circulation (2022)

Introduction: Elevated Lipoprotein(a) (Lp[a]) levels are strongly and linearly associated with coronary artery disease (CAD) and calcific aortic valve stenosis (CAVS). Observational studies in primary and secondary prevention settings revealed that Lp(a) and other CAD risk factors such as C-reactive protein (CRP) levels, a biomarker of systemic inflammation, may jointly predict CAD risk. Whether Lp(a) and CRP levels also jointly predict CAVS risk is unknown. Methods: We investigated the long-term associations of Lp(a) with CAD and CAVS according to CRP levels in the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Norfolk study. Lp(a) and CRP levels were measured in 18,459 participants who were followed for 20 years. During the follow-up, 3915 and 418 participants had incident CAD and CAVS, respectively. Results: As presented in Figure 1, in comparison to individuals with low Lp(a) levels (&lt;30 mg/dL) and low CRP levels (&lt;2.0 mg/dL), those with elevated Lp(a) (&gt;30 mg/dL) and low CRP levels (&lt;2.0 mg/dL) and those with elevated Lp(a) (&gt;30 mg/dL) and elevated CRP levels (&gt;2.0 mg/dL) had a higher CAD risk (hazard ratio [HR] = 1.38 [95% CI, 1.28-1.49] and 1.93 [95% CI, 1.74-2.13] , respectively), and a higher CAVS risk (HR = 1.46 [95% CI, 1.08-1.98] and 1.87 [95% CI, 1.40-2.49], respectively). Conclusions: Results of this study confirm the joint association of high Lp(a) and CRP levels on incident CAD and extend these joint associations to valvular diseases such as CAVS. Lowering Lp(a) levels may warrant further investigation in the prevention of CAD and CAVS, especially in the context of systemic inflammation.
Abstract 10753: Phosphodiesterase Type 5 Inhibition and C-c Chemokine Receptor-2 Disruption Synergistically Protect Against Pulmonary Arterial Hypertension in Monocrotaline-Treated Rats: Potential Synergism of Anti-inflammatory Agents and Pulmonary Vasodilator Therapy
Authors: NAOKI TSUBOYA, Yoshihide Mitani, Hirofumi Sawada, Hironori Oshita, Kazunobu Ohya, Noriko Yodoya, Hiroyuki Ohashi, Kazuo Maruyama, Masahiro Hirayama
Journal: Circulation (2022)

BACKGROUND: Whether conventional pulmonary vasodilator therapy and anti-inflammatory agents synergistically protect against pulmonary arterial hypertension (PAH) is unknown. Hypothesis: We tested the hypothesis that a phosphodiesterase type 5 (PDE5) inhibitor and disruption of C-C chemokine receptor (CCR)-2, a receptor for MCP-1, synergistically protect against PAH in monocrotaline (MCT)-treated rats. Methods: Study1:Seven-week-old male Ccr2 (-/-) rats, generated by using the CRISPAR/ Cas9 genome editing technology, or wild-type littermates, treated with MCT (60mg/kg) or vehicle, were subjected to hemodynamic, morphometric and immunohistochemical analyses and mRNA and protein expression studies on day21 (n=40, 4 groups). Study 2: Tadarafil (10mg/kg/d), a PDE5 inhibitor, or vehicle was administered in Ccr2 (-/-) or wild-type MCT rats on days 21-42 (n=71, 4 groups) for evaluating survival and were evaluated hemodynamically on day28. Results: Study1: MCT treatment increased right ventricular systolic pressure (RVSP), an index of right ventricular hypertrophy (Fulton index), indices of pulmonary vascular diseases (%medial wall thickness, %muscularization) and the number of perivascular CD68-positive macrophages in WT rats, all of which were decreased by Ccr2 (-/-) (p&lt;.05). Similarly, an increase in mRNA expression of inflammatory cytokines (IL6 ,TNFa, MCP1, IL1b, TGFb) and a decrease in BMPR2 pathways (BMPR2, pSmad1/5/9 and ID1) as well as an increase in endothelial apoptosis (% cleaved Caspase 3 positive CD31 cells) and a decrease in NO pathways (eNOS and phospho-eNOS/eNOS) in lungs in wild-type MCT rats were reversed by Ccr2 (-/-) on day21 (p&lt;.05) with comparable PDE5 expression. Study2: Tadarafil administration or CCR2(-/-)(p=.03 and p=.02) alone improved the survival in wild type MCT rats. A double intervention synergistically improved the survival in separately treated groups (p=.02 vs CCR2(-/-), p=.04 vs Tadarafil) in MCT rats. Tadarafil treatment on days21-28 decreased RVSP and Fulton index in CCR2(-/-) MCT rats (p&lt;.05). Conclusions PDE5 inhibition and CCR-2 disruption synergistically protect against PAH in MCT-treated rats, suggesting an adjunctive role of a CCR2 inhibitor on top of administering a PDE5 inhibitor for PAH.
Abstract 10938: Concomitant Latent Pulmonary Vascular Disease Leads to Impaired Global Cardiac Performance in Heart Failure With Preserved Ejection Fraction
Authors: Andreas Schuster, Alexander Schulz, Torben Lange, Ruben Evertz, Finn Hartmann, Johannes Kowallick, Kristian Hellenkamp, Martin Uecker, Tim Seidler, Gerd Hasenfuss, Soeren J Backhaus
Journal: Circulation (2022)

Introduction: The REDUCE-LAP II trial demonstrated adverse outcomes after interatrial shunt device (IASD) placement in heart failure with preserved ejection fraction (HFpEF) attributed to latent pulmonary vascular disease (PVD). We hypothesized that exercise-stress cardiovascular magnetic resonance (CMR) imaging could provide non-invasive characterisation of cardiac and pulmonary physiology for improved patient selection. Methods: The HFpEF-Stress Trial prospectively enrolled 75 patients with exertional dyspnoea and diastolic dysfunction. Patients underwent rest and exercise-stress right heart catheterisation (RHC), echocardiography and CMR imaging. Pulmonary artery and capillary wedge pressures, cardiac index (CI) and vascular resistance (PVR) were calculated. Latent PVD was defined as increased PVR≥1.74 Wood-Units during exercise-stress. CMR assessed long axis strains (LAS) and filling volumes of all cardiac chambers. Right ventricular (RV) function was further quantified by stroke and peak flow volumes. Results: Patients with latent PVD (n=24) showed higher HFA-PEFF scores and lower RV function (rest TAPSE, p=0.010; stress RV LAS, p&lt;0.001) compared to patients without (n=43). RV filling (p=0.007), stroke and peak flow volumes (p&lt;0.001) were reduced and led to impaired left atrial (p≤0.010) and ventricular (LV) filling (p≤0.008) and LV-CI (p&lt;0.001) despite normal LV contractility (LV LAS p≥0.255). The degree of RV dysfunction during exercise-stress best predicted latent PVD (RV peak flow, AUC rest 0.81 vs. stress 0.91, p=0.005). Conclusions: Latent PVD is a feature of advanced HFpEF and associated with impaired RV functional reserve, global diastolic filling and LV-CI. This can be quantified by CMR and used to identify patients likely to benefit from IASD implantation.
Abstract 10669: Phenytoin, an Anti-Epileptic Sodium Channel Blocker, May Be a Novel Therapy for Type 3 Long Qt Syndrome Mediated by the Lidocaine-Insensitive SCN5A-F1760C Variant
Authors: Dan Ye, Marissa Stutzman, Maengjo Kim, Martina Gluscevic, Wei Zhou, Xiaozhi Gao, David J Tester, John Giudicessi, Kevin Shannon, Michael J Ackerman
Journal: Circulation (2022)

Introduction: Gain-of-function mutations in SCN5A- encoded cardiac sodium channel (Na V 1.5) cause type 3 long QT syndrome (LQT3). Patients with SCN5A variants localizing to the local anesthetic binding domain might not be sensitive to lidocaine or mexiletine treatment. Hypothesis: Phenytoin, a sodium channel blocker used to treat epilepsy, may be a novel LQT3-directed therapy for a variant involving a critical residue of the Nav1.5’s local anesthetic binding domain. Methods: SCN5A-F1760C was identified in a now deceased infant with severe LQT3 (QTc of 680-1200 ms) who was refractory to left cardiac sympathetic denervation and pharmacological treatments with either lidocaine or mexiletine. SCN5A-F1760C was engineered by site directed mutagenesis and expressed in TSA201 cells. Patient-specific pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from the SCN5A-F1760C-positive infant and gene-edited/variant-corrected isogenic control (IC) iPSC-CMs were generated. Na V 1.5 currents were recorded in TSA201 cells transfected with SCN5A-WT/ F1760C and action potentials (APs) from iPSC-CMs were recorded before and after treatment with 5μM Phenytoin using the whole cell patch-clamp technique. Results: SCN5A-F1760C did not change the NaV1.5 current density. However, the V1/2 of inactivation was right-shifted significantly by +14.1 mV from -86.3±0.9 mV (WT) to -72.2±0.7 mV (F1760C, p&lt;0.0001) resulting in a marked increase in window current. F1760C increased sodium late current 2-fold from 0.18±0.04% in WT to 0.49±0.07% in F1760C (p=0.0005). Baseline APD to 90% repolarization (APD90) was prolonged significantly in F1760C-derived iPSC-CMs (641±40 ms) compared to IC iPSC-CMs (412±22 ms, p&lt;0.0001). Treatment with 5μM phenytoin normalized the APD90 in F1760C-derived iPSC-CMs to 423+34 ms (p&lt;0.0001), values approximating the ‘gene/variant-edited’ cure. Conclusions: Na V 1.5 gain-of-function caused by a novel SCN5A-F1760C variant results in marked APD90 prolongation which were rescued by phenytoin indicating the antiepileptic drug, phenytoin, may be a mutation-specific, LQT3-directed therapy for those LQT3-causative variants that disrupt the local anesthetic/lidocaine-binding domain.
Abstract 10034: Novel Late-Gadolinium Enhanced Cardiac Magnetic Resonance (LGE-CMR)-Based Computational Heart Paradigm Predicts Optimal Ventricular Tachycardia (VT) Ablation Targets in Arrhythmogenic Right Ventricular (RV) Cardiomyopathy (ARVC)
Authors: Yingnan Zhang, Adityo Prakosa, Eric Sung, Alessio Gasperetti, Richard Carrick, Cynthia James, Stefan Zimmerman, Crystal Tichnell, Brittney Murray, Hugh G Calkins, Harikrishna S Tandri, Natalia Trayanova
Journal: Circulation (2022)

Introduction: ARVC is an inherited cardiac disease that increases risk of life-threatening VTs in young adults. Catheter ablation, a mainstay of VT treatment in ARVC, remains challenging due to difficulties in identifying optimal VT ablation targets. Hypothesis: Right Ventricular Cardiomyopathy Ablation Targeting (RVCAT) is a novel digital-heart paradigm that accurately predicts the optimal VT ablation targets of ARVC patients. Methods: We retrospectively enrolled 11 ARVC patients; 8 presented with clinical VTs and underwent VT ablation. In all patients, RV hyperenhancement on LGE-CMR was identified. For this study, we developed RVCAT, the first computational heart model integrating RV personalized diffuse and dense fibrosis as VT substrates. Each region was assigned ARVC-specific electrophysiologic properties. VT inducibility was assessed via rapid pacing in each model. If inducible, optimal ablation targets, which rendered the RV substrate non-inducible for each VT, were determined. Targets were compared to electroanatomic voltage maps (EAM), locations of clinical ablations, and clinical records. Results: Personalized model predictions correlated well with clinical observations. All 8 models of the patients with a history of clinical VT had inducible VTs (Fig A). Furthermore, model VT circuit locations matched the clinical description. Substrate distribution in models matched low-voltage zones in EAM. The predicted ablation targets coincided with clinical ablations (Fig B). Results showed that the volume of model ablation lesions was significantly smaller than that of clinical ablations (1.02±0.68 versus 1.45±0.91, p&lt;0.05, Fig C). For the 3 patients who did not have VTs, their corresponding heart models correctly predicted that no VTs would be induced. Conclusions: RVCAT is a novel digital-heart technology for optimal ARVC VT ablation guidance that can be potentially integrated into clinical workflows for augmenting therapeutic precision.
Abstract 10442: Protective Effect of Inhibition of Sglt2 on Nanoplastics-Induced Premature Endothelial Senescence and Dysfunction
Authors: Bikalpa Dhakal, Saugat Shiwakoti, Ju-Young Ko, KI-WOON KANG, Valerie Schini-Kerth, Min-Ho Oak
Journal: Circulation (2022)

Background: Nanoplastics (NPs) are now widely acknowledged as a vital part of environmental pollution. However, the effects of NPs on the cardiovascular system are not well understood. We previously reported that NPs induce premature endothelial senescence and dysfunction via a redox-sensitive signaling pathway. Increasing evidence has shown that SGLT2 inhibitors (gliflozins) exhibit protective effects against the development of major cardiovascular diseases. Objective: This study aimed to investigate the role of SGLT2 on NPs-induced premature endothelial senescence and dysfunction, and, if so, to assess the effect of SGLT2 inhibition. Methods: Porcine coronary artery (PCA) rings and cultured endothelial cells (ECs) were exposed to NPs in the presence or absence of the SGLT2 inhibitor, Enavogliflozin (ENA), and the level of SGLTs expression, senescence-associated-beta galactosidase (SA-β-gal) activity, senescence markers, oxidative stress level, and vascular function were evaluated. Results: NPs were internalized in ECs in a time- and concentration-dependent manner. Exposure of PCAECs to NPs significantly up-regulated SGLT2 expression and increased SA-β-gal activity, one of the prominent senescence markers. ENA significantly reduced the NPs-induced increase of SA-β-gal activity in PCA and PCAECs. In addition, ENA prevented the NPs-induced up-regulation of senescence markers, p53, and p21 that promoted the inhibition of ECs proliferation. ENA prevented also the NPs-induced oxidative stress and up-regulation of NOX2 and p22phox in ECs. Exposure of coronary artery rings to NPs blunted endothelium-dependent relaxation and decreased the expression level of endothelial nitric oxide synthase level, and both of these effects were prevented by ENA. Conclusion: The present findings indicate that premature endothelial senescence and dysfunction induced by nanoplastics involve, at least in part, an upregulation of SGLT2, which is associated with increased levels of oxidative stress and the down-regulation of eNOS. They further raise the possibility that SGLT2 may be a potential target for preventing and/or treating environment pollution-associated cardiovascular diseases.
Abstract 10345: Comparison of Clinical Characteristics, Positive Airway Pressure Usage, and Healthcare Resource Utilization in Obstructive Sleep Apnea Patients With Heart Failure With Preserved vs Reduced Ejection Fraction
Authors: Fatima H Sert Kuniyoshi, Atul Malhotra, Kate V Cole, Anita Malik, Jean-Louis Pépin, Peter A Cistulli, Adam V Benjafield, Virend K Somers
Journal: Circulation (2022)

Introduction: The prevalence of obstructive sleep apnea (OSA) in heart failure (HF) patients varies from 30 to 50%. The differences in clinical characteristics, healthcare resource utilization (HCRU), and positive airway pressure (PAP) usage between HF with preserved ejection fraction (HFpEF) vs. HF with reduced ejection fraction (HFrEF) in OSA patients are not well known. Objective: To compare clinical characteristics, PAP usage, and HCRU in OSA patients with HFpEF vs HFrEF. Methods: Retrospective cohort study using US administrative claims data linked to objective PAP usage data over one year. HFpEF and HFrEF were identified by ICD-9/10 codes associated with healthcare encounters 1 year before starting PAP therapy. Pearson’s Chi-squared and Wilcoxon rank-sum tests were used as applicable to compare baseline characteristics and PAP usage, and the pre to post-PAP initiation difference in the number of health care encounters. Results: In total, 7,419 patients with HF and OSA were identified, of which 57% had HFpEF. HFpEF patients were majority female (54%) and older than those with HFrEF (64.1 ± 11.52 vs 59.7 ± 11.24 years, p&lt;0.001). HFpEF had a higher overall comorbidity burden, although coronary artery disease, atrial fibrillation, and other arrhythmias were more prevalent in HFrEF. Both prior to and after PAP therapy, HCRU was higher in HFpEF patients compared to HFrEF (Table 2a). There were no differences in PAP usage between HFpEF and HFrEF (3.6 ± 2.9 vs 3.7 ± 3.0 hrs/night, p=0.070) over the first year of PAP therapy. There was a significant reduction in ER visits and all cause hospitalizations after 1 year of PAP therapy initiation, which was similar between groups (Table 2b). Conclusions: Although there were differences in clinical characteristics between HFpEF and HFrEF patients with OSA, and HFpEF is associated with greater HCRU, PAP therapy usage was similar, and both groups experienced a similar reduction in HCRU after the first year of PAP initiation.
Abstract 10282: Early Anticoagulation Improves Post-Thrombotic Syndrome Outcomes and Experimental Restoration of Blood Flow in DVT Subjects
Authors: Wenzhu Li, Dawei Wang, Hang Lee, Guoping Li, Saumya Das, Ido Weinberg, Rachel Rosovsky, Guy L Reed, Peter Libby, Ahmed A Tawakol, Peter Henke, Farouc A Jaffer
Journal: Circulation (2022)

Introduction: Despite anticoagulation (AC), up to 50% of proximal deep vein thrombosis (DVT) patients will develop the post-thrombotic syndrome (PTS). In a substudy of the ATTRACT DVT trial, catheter-directedthrombectomy/thrombolysis (CDT) in addition to AC improved PTS outcomes for patients presenting at an intermediate day (D) 4-8 symptom-onset-to-randomization (SOR) timeframe, but not at an early D0-3 or late D9+ SOR timeframe. Mechanisms underlying the role of early AC and CDT are unknown, particularly iliofemoral DVT (IFDVT) patients that preferentially benefit from CDT. Methods: First, we assessed the temporal impact of AC on Villalta and VEINES-QoL PTS scores in a post-hoc analysis of the IFDVT ATTRACT patients (N=391). Mean scores were estimated by a piecewise linear-regression growth-curve model. Next, to mechanistically explore the effects of AC on PTS measures, C57/BL6 mice (N=76) underwent inferior vena cava (IVC) ligation to produce stasis DVT. Mice then underwent true or sham de-ligation at D2 to spur restoration of blood flow (RBF). Last, enoxaparin AC was initiated at D2 and given daily until D8, at either 0, 10, or 30 mg/kg/d SQ. D4 RBF rates in the IVC, and D8 thrombus burden were assessed. Results: In IFDVT ATTRACT patients, CDT+AC improved PTS scores in the intermediate D4-8 SOR timeframe (p&lt;0.001 vs. AC alone). However, in the early D0-3 SOR timeframe, CDT+AC did not improve PTS scores (p&gt;0.05 vs. AC alone). In the AC alone groups, early AC D0-3 significantly improved PTS scores over delayed AC (p&lt;0.05). In sham de-ligated mice with IVC DVT, D2 enoxaparin improved D4 RBF rates (sham, 11.1%; low-dose, 33.3%; high-dose, 40.0%). D2 enoxaparin also significantly reduced D8 thrombus weight (p&lt;0.05, both doses vs. saline). However, in true de-ligation mice, D2 enoxaparin only mildly increased D4 RBF rates (sham, 50%; low-dose, 61.5%; high-dose, 60%), and did not decrease D8 thrombus weight (p&gt;0.05). Conclusions: In ATTRACT patients presenting with IFDVT at an early D0-3 SOR timeframe, PTS outcomes were improved by AC but not further improved by CDT. Experimentally, early D2 AC initiation can improve RBF rates and DVT resolution. These findings suggest that achieving early RBF may reduce the risk of PTS.